Phosphoproteome analysis reveals differences in phosphosite profiles between tumorigenic and non-tumorigenic epithelial cells

Autor(es)

Winck, Flavia V. ^[1] ; Belloni, Marilia ^[1] ; Pauletti, Bianca A. ^[1] ; Zanella, Jackeline de Lima ^[1] ; Domingues, Romenia R. ^[1] ; Sherman, Nicholas E. ^[2] ; Paes Leme, Adriana F. ^[1]

Afiliação do(s) autor(es)

^[1] CNPEM, LNBio, Lab Nacl Biociencias, BR-13083970 Campinas, SP - Brazil

^[2] Univ Virginia, Sch Med, Charlottesville, VA 22908 - USA

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF PROTEOMICS; v. 96, p. 67-81, JAN 16 2014.
• Citações Web of Science: 8

Resumo

Oral cancer disease represents a significant fraction of all human cancer types and its poor early diagnosis contributes to reduced individual survival rate. The identification of proteins modulated in tumorigenic cells and its post-translational modifications may improve our understanding of tumor development in epithelial cells. We have analyzed the phosphoproteome of tumorigenic (SCC-9) and non-tumorigenic (HaCaT) cell lines using MS-based approach in order to identify phosphopeptides with differing patterns of modifications and/or abundance. Our results revealed the identity of 4,206 protein phosphorylation sites with sixty-two sites showing to be significantly modulated between the two cell lines. The phosphoproteome data showed an overrepresentation of proteins with a possible role in nuclear regulatory functions. Pathway analysis was further performed on the phosphoproteome dataset and differences and commonalities of the functional pathways present in tumorigenic and non-tumorigenic cells were identified. Phosphopeptides that belong to the proteins lamina-associated polypeptide 2 isoform alpha and serine arginine repetitive matrix protein 2 were identified with differential abundance and they appear as promising tumor-related phosphopeptides. These two proteins may be related to the structural alterations generally found in the nucleus of tumorigenic cells. The identification of phosphorylation sites in tumorigenic cells may contribute to disclose novel signaling mechanisms associated with OSCC. Significance Oral Squamous Cell Carcinoma (oscq is an important cancer disease affecting thousands of people worldwide. Many cellular processes related to the development of oral cancer remain unknown; however, the studies performed in vitro with cancer cells have contributed to guide more specific research which may be further performed by using in vivo approaches or clinical samples. To our knowledge, only few studies have been published showing the results of phosphoproteome profiling of squamous cell carcinoma models, and many signaling proteins must be identified and functionally characterized in order to increase the knowledge available about the complexity of the signaling networks responsible for oral cancer development and its progression. Furthermore, our knowledge regarding proteins exclusive or very low abundant in cancer cells remains limited. A better understanding of the differences between signaling pathways present in epithelial cell lines may contribute to reveal the processes underlying the OSCC. (C) 2013 Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 09/54067-3 - EMU: aquisição de um espectrômetro de massas acoplado a cromatografia líquida para permitir ampliar a capacidade de atendimento de usuários e disponibilizar novas tecnologias no Laboratório de Espectrometria de Massas do Centro de Biologia Molecular Estrutural (ABTLUS)
• Beneficiário: Adriana Franco Paes Leme
• Linha de fomento: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
• Processo FAPESP: 09/52833-0 - Análise diferencial de proteínas e peptídeos extracelulares em carcino ma de células escamosas e células normais utilizando abordagem de proteômica
• Beneficiário: Marília Belloni
• Linha de fomento: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 10/19278-0 - Estudo da regulação de ADAMs em câncer oral
• Beneficiário: Adriana Franco Paes Leme
• Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores